: In addition to providing ligands for T cell receptor engagement, antigen presenting cells (APCs) direct the activation and differentiation of T cells by providing costimulatory signals. One of the most important families of costimulatory molecules is the B7 family, which currently consists of 4 members, each of which appears to be important in mediating various aspects of T cell dependent immune responses. Dendritic cells (DCs), unique APCs with potent T cell stimulatory capacity, are critical modulators of both natural and vaccine induced immune responses. We have cloned a new B7 family member, termed B7-DC, whose expression is highly restricted to DCs. B7-DC was identified among a library of genes differentially expressed between DCs and activated macrophages. B7-DC costimulates T cell proliferation more efficiently than B7-1 and induces a distinct pattern of lymphokine secretion, characterized by high levels of the proinflammatory lymphokines, gamma-interferon (g-IFN) and interleukin-6 (IL-6). These properties of B7-DC may account for some of the unique activity of DCs relative to other APCs. The current application seeks to define the biologic role of B7-DC in mediating immune responses. Specifically, we plan to: 1) Quantitatively determine the expression pattern of B7-DC and which signals induce its expression, 2) Perform a detailed analysis of B7-DC's costimulatory activity in vivo, 3) Analyze its in vivo role in mediating immune responses, 4) Identify receptor(s) for B7-DC and 5) Determine whether human B7-DC functions similarly to murine B7-DC.
